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Assessment of xenoestrogens in the Australian freshwater environment: use, development and validation of in-vitro and in-vivo modelsWoods, Marianne January 2007 (has links)
Xenoestrogens are chemical pollutants that can disrupt the endocrine system of animals by binding to and activating the estrogen receptor(s). They include both natural and synthetic steroid estrogens, together with a variety of estrogen mimicking chemicals such as 4-nonylphenol, bisphenol A and various pesticides. In vertebrates, estrogens play a fundamental role in reproduction, in somatic cell function, the regulation of calcium and water homeostasis. Exposure to xenoestrogens may therefore have unscheduled effects on these systems that can potentially compromise species survival. With the ever-increasing number of xenoestrogens identified and detected in the environment, together with the fact that they are seldom detected alone, there is a need to develop specific and sensitive biomarkers to detect estrogenic activity of chemicals in the environment when present alone and in mixtures. In this study, the effect of selected xenoestrogens was assessed using an in-vitro yeast estrogen screen (YES) both individually and in mixtures and in-vivo in a native fish species, the Murray rainbowfish (Melanotaenia fluviatilis).
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PRESENCE OF ADP-RIBOSYLATION FACTOR 1 (ARF1) IN THE CHOROID PLEXUS: IMPACT ON COPPER LEVELS IN THE CEREBROSPINAL FLUID AND LEAD EXPOSURETianyuan L Sang (15363724) 29 April 2023 (has links)
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<p>Copper (Cu) dyshomeostasis in the brain, especially Cu overload, has been associated with neurodegenerative disorders such as Alzheimer’s disease (AD). Brain Cu levels are partly regulated by the choroid plexus (CP), a tissue that forms a barrier between the blood and cerebrospinal fluid (CSF) and is rich in Cu-transporting proteins. Literature data have shown that ADP-ribosylation factor 1 (ARF1) plays a role in regulating cellular Cu homeostasis; yet its presence and function in the blood-CSF barrier was unknown. The main purpose of the project was to prove the presence of ARF1 in the CP and explore its possible function with regards to Cu regulation. Since the CP is known to accumulate toxic metal lead (Pb) from human and animal studies, the project also aimed to test whether Pb exposure caused CSF Cu dyshomeostasis through disrupting ARF1-mediated Cu regulatory mechanism. Using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC), our data clearly demonstrated that ARF1 was highly enriched in the choroidal epithelial Z310 cells and expressed in CP tissues. Acute Pb exposure in mice (one ip. dose at 27 mg Pb/kg followed by tissue dissection 24 hrs later) significantly increased ARF1 expression in the CP as compared to saline-injected controls, suggesting a high responsiveness of the protein to Pb exposure. In the subsequent chronic study, mice were exposed to Pb via drinking water at 200ppm (low-dose) or 800ppm (high-dose) at libitum for 4 weeks (control group had sodium in drinking water). Atomic absorption spectrometry (AAS) analyses verified a dose-dependent Pb accumulation in the CP. Importantly, Cu concentrations in the CSF displayed a Pb dose-dependent increase as compared to controls. IHC data further revealed an altered ARF1 expression in the choroidal epithelia in chronic Pb exposed animals. Further knocking down ARF1 expression in choroidal epithelial Z310 cells using in vitro Arf1-targeting siRNA transfection approach revealed a decreased Cu level in cells, suggesting a critical role of ARF1 in cellular Cu regulation. In choroidal epithelial cells exposed to Pb in culture medium, a down-regulated ARF1 expression partly reversed Pb-induced Cu overload. Taken together, this study provides first-hand evidence to support the presence of ARF1 in the blood-CSF barrier. Further, our data demonstrate that Pb exposure causes Cu overload in the CSF, which is likely mediated by an altered expression of ARF1 in the blood-CSF barrier.</p>
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The role of peroxisome proliferator-activated receptors in the rat brainSmith, S. Unknown Date (has links)
No description available.
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The role of peroxisome proliferator-activated receptors in the rat brainSmith, S. Unknown Date (has links)
No description available.
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The role of peroxisome proliferator-activated receptors in the rat brainSmith, S. Unknown Date (has links)
No description available.
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Developmental Toxicity of Sodium Iodide Using the Zebrafish ModelBrian A Sumprer (9757382) 14 December 2020 (has links)
<p>Iodine is considered an essential nutrient as lack can cause
severe metabolic and neurological issues in adults, with the added consequence
of permanent developmental damage in children and infants. However, excessive
iodine intake can result in similar symptoms, with a wide variance in adverse
health outcomes. The safe range of iodine intake may be relatively low, with
some studies suggesting the possibility of a high frequency of subclinical
cases of iodine poisoning going unnoticed or misdiagnosed. </p>
<p>In this study, the zebrafish model was tested as an
integrative whole animal model to demonstrate behavioral, morphological, and
genetic responses to overt and subclinical iodine poisoning in developing
humans. Zebrafish embryos were treated with sodium iodide (NaI) immediately
after fertilization. Survivability was monitored every 24 hours until 120 hours
post fertilization (hpf). Concentrations with no statistical significance on
survival, plus the smallest dose of significant lethality were then examined
using behavioral analysis at 120 hpf to compare both overt and subclinical
outcomes. Morphology measurements of body length, head length, head width,
brain length, swim bladder volume, jaw length, and ventral dissension were also
recorded at 120 hpf. Gene expression of <i>slc5a5</i>,
<i>tpo</i>, and <i>tshba</i> at 72 hpf was also measured using quantitative PCR (qPCR). </p>
<p>A significant decrease in survival rates were observed at 24
hpf for 25, 37.5, and 50 mM NaI treatments (p<0.0001). Morphological
measurements taken at 120 hpf showed a significant increase in body length,
head length, head width, jaw length, and swim bladder volume in the 10 mM NaI
treatment group (p<0.0001) and a significant decrease in body length, head
length, jaw length, and swim bladder volume in the 25 mM treatment group
(p<0.0001). A ventral distension also developed near the location of the
thyroid gland exclusively in the 25 mM group. </p>
<p>Behavioral analysis showed significant increases in movement
for both the 10 mM and 25 mM treatment groups during dark phases (p<0.0001).
The 25 mM treatment group had an increase in movement during dark phases for
standard well environments (p<0.0001), but this did not hold true for larger
well environments, instead trending towards a non-significant decrease
(p>0.05). The 10 mM group had a significant decrease during the first light
phase in standard wells (p=0.002), with a significant increase in the second
light phase for large wells (p=0.005). There were no significant changes in the
expression of selected genes associated with the thyroid pathway (<i>slc5a5</i>, <i>tpo</i>, or <i>tshba</i>) across all
treatment groups (p>0.05). </p><p><br></p>
<p>Overall, the results suggest zebrafish larvae exhibit both
overt and subclinical symptoms of excess iodine intake. Future studies are
needed to determine internalization, biodistribution, clearance, and further characterization
of adverse outcomes along the thyroid pathway for additional exploration into
subclinical thyrotoxicosis due to excess iodine intake. Researchers should
express caution with time points, as the Wolff-Chaikoff effect may influence
exposure windows in zebrafish. </p>
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<strong>Demonstration of Choroid Plexus-Subventricular Zone Regulatory (CSR) Axis Mediated by Small Extracellular Vesicles: Toxicological, Molecular, and Neurobehavioral Characterizations</strong>Luqing Liu (15363706) 29 April 2023 (has links)
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<p>The choroid plexus (CP) in brain ventricles secrete cerebrospinal fluid (CSF) that bathes the adjacent subventricular zone (SVZ); the latter is the largest neurogenic region in adult brain harboring neural stem/progenitor cells (NSPCs) and supplies newborn neurons to the olfactory bulb (OB) for normal olfaction. We discovered the presence of a CP-SVZ regulatory (CSR) axis in which the CP, by secreting small extracellular vesicles (sEVs), regulated adult neurogenesis in the SVZ and maintained olfaction. The proposed CSR axis was supported by 1) differential neurogenesis outcomes in the OB when animals treated with intracerebroventricular (ICV) infusion of sEVs collected from the CP of normal or manganese (Mn)-poisoned mice, 2) progressively diminished SVZ adult neurogenesis in mice following CP-targeted knockdown of SMPD3 to suppress CP sEV secretion, and 3) compromised olfactory performance in these CP-SMPD3-knockdown mice. Collectively, our findings demonstrate the biological and physiological presence of this sEV-dependent CSR axis in adult brains.</p>
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Studies of coagulation and fibrinolysis using Australian snake venoms: From molecular toxicology to novel therapeutic agentsMasci, P. Unknown Date (has links)
No description available.
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The initiation of autoimmune reactions in anticonvulsant drug-induced hypersensitivity: The role of cytochrome P450 enzymesKinobe, R. Unknown Date (has links)
No description available.
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Studies of coagulation and fibrinolysis using Australian snake venoms: From molecular toxicology to novel therapeutic agentsMasci, P. Unknown Date (has links)
No description available.
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